HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury.
HLA-A Locus is Associated With Sepsis and Septic Shock After Traumatic Injury.
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DOI：
10.1097/sla.0000000000003932
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发表时间：
2022-01-01
影响因子：
9
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中科院分区：
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确定人类白细胞抗原区域的变异是否与创伤后脓毒症和感染性休克的发生有关。脓毒症相关死亡仍然是创伤后死亡的主要来源。遗传特征可能导致败血症和感染性休克等不良结局的易感性。新一代测序技术的最新进展现在允许对人类白细胞抗原区域进行全面的基因分型。需要2天以上机械通气的白人成人创伤患者接受了人类白细胞抗原基因分型，并跟踪观察了脓毒症和感染性休克的发生。我们评估了我们的结果与人类白细胞抗原变异之间的关联的优势比(OR)，对多重比较进行了校正，并将显著的变异包括在对潜在混杂因素进行调整的回归模型中。共纳入1184名患者。患者严重受伤(中位损伤严重程度评分33)；33%发生败血症，6%败血症休克，住院死亡率为14%。人类白细胞抗原-A肽结合沟内的氨基酸变异(156Q)与脓毒症的发生几率较高[OR1.50，(1.18-1.89)]。HLA-A*02：01与感染性休克的发生几率较低[OR0.52，(0.32~0.82)]。在对潜在的混杂因素进行调整后，这些关联仍然显著。这是应用下一代测序技术评估免疫遗传因素与创伤后脓毒症和感染性休克之间的关系的第一项研究。与I类人类白细胞抗原变异的关联是新的，因为它们与创伤后脓毒症的适应性免疫有关。随着我们走向更加个性化的医学，这些发现是朝着开发一组评估感染相关并发症风险的遗传标记迈出的一步。
Determine whether variation in the HLA region is associated with the development of post-traumatic sepsis and septic shock. Sepsis-related deaths remain a major source of mortality after traumatic injury. Genetic characteristics may contribute to susceptibility to adverse outcomes including sepsis and septic shock. Recent advances in next-generation sequencing technology now allow comprehensive genotyping of the HLA region. White adult trauma patients requiring more than 2 days of mechanical ventilation underwent HLA genotyping, and were followed for the development of sepsis and septic shock. Odds ratios (OR) for the associations between our outcomes and HLA variants were estimated, a correction for multiple comparisons was applied, and significant variants were included in regression models adjusting for potential confounders. A total of 1184 patients were included. Patients were severely injured (median injury severity score 33); 33% developed sepsis, 6% septic shock, and in-hospital mortality was 14%. An amino acid variant (156Q) within the HLA-A peptide-binding groovewas associated with greater odds of sepsis [OR 1.50, (1.18–1.89)]. HLA-A*02:01 was associated with lower odds of septic shock [OR 0.52, (0.32–0.82)]. These associations remained significant after adjusting for potential confounders. This is the first study to apply next-generation sequencing techniques to evaluate associations between immunogenetic factors and post-traumatic sepsis and septic shock. Associations with class I HLA variants are novel as they implicate adaptive immunity in post-traumatic sepsis. These findings are a step towards developing a panel of genetic markers assessing risk of infection-related complications as we move towards more personalized medicine.